Leishmaniasis affects 12 million people worldwide, with an estimated 2 million new infection occurring annually. All four main forms of disease, visceral (VL), cutaneous (CL), disseminated (DL) and mucosal leishmaniasis (ML), are prevalent in our study areas in the Northeast of Brazil. The main objective of this program is to expand and translate the knowledge acquired in the host parasite relationship in leishmaniasis to improve diagnose, establish new forms of therapy and to control leishmaniasis. The Federal University of Bahia (UFBA) Tropical Medicine Research Center was established in 1991. The Federal University of Rio Grande do Norte joined the TMRC in 1996 to share their expertise in VL. Strong collaborative programs have been established between Brazilian and US universities in Tropical diseases. This proposal entitled Host and Parasite Determinants in Human Leishmaniasis has 4 cores (administrative, data management, epidemiology and transcriptomics) and 3 scientific projects. Project I Polymorphic features of Leishmania braziliensis: disease manifestations, geographic distribution, and genomes will be use molecular and epidemiological tools to improve diagnosis associating genotype of parasite with clinical forms of leishmaniasis, as well as to identify isolates resistant to antimony therapy. Project II Protective and pathological immune response In L. braziliensis infection will address the role of innate Immunity in control L. braziliensis infection in individuals with subclinical L. braziliensis infection as well as the role of CD8+T cells and macrophages in the pathology of American Tegumentary Leishmaniasis. Project III Genetic and Environmental Determinants of Symptomatic and Asymptomatic Leishmaniasis will determine host genetic determinants affecting the outcome of visceral and tegumentary leishmaniasis, will perform transcriptome profiling of blood of VL patients in order to identify potential markers of progression or control f leishmania infection.